Elsevier

The Lancet

Volume 388, Issue 10047, 27 August–2 September 2016, Pages 906-918
The Lancet

Seminar
Hyperthyroidism

https://doi.org/10.1016/S0140-6736(16)00278-6Get rights and content

Summary

Hyperthyroidism is characterised by increased thyroid hormone synthesis and secretion from the thyroid gland, whereas thyrotoxicosis refers to the clinical syndrome of excess circulating thyroid hormones, irrespective of the source. The most common cause of hyperthyroidism is Graves' disease, followed by toxic nodular goitre. Other important causes of thyrotoxicosis include thyroiditis, iodine-induced and drug-induced thyroid dysfunction, and factitious ingestion of excess thyroid hormones. Treatment options for Graves' disease include antithyroid drugs, radioactive iodine therapy, and surgery, whereas antithyroid drugs are not generally used long term in toxic nodular goitre, because of the high relapse rate of thyrotoxicosis after discontinuation. β blockers are used in symptomatic thyrotoxicosis, and might be the only treatment needed for thyrotoxicosis not caused by excessive production and release of the thyroid hormones. Thyroid storm and hyperthyroidism in pregnancy and during the post-partum period are special circumstances that need careful assessment and treatment.

Introduction

Hyperthyroidism is a pathological disorder in which excess thyroid hormone is synthesised and secreted by the thyroid gland. It is characterised by normal or high thyroid radioactive iodine uptake (thyrotoxicosis with hyperthyroidism or true hyperthyroidism). Thyrotoxicosis without hyperthyroidism is caused by extrathyroidal sources of thyroid hormone or by a release of preformed thyroid hormones into the circulation with a low thyroid radioactive iodine uptake (table 1).1 Hyperthyroidism can be overt or subclinical. Overt hyperthyroidism is characterised by low serum thyroid-stimulating hormone (TSH) concentrations and raised serum concentrations of thyroid hormones: thyroxine (T4), tri-iodothyronine (T3), or both. Subclinical hyperthyroidism is characterised by low serum TSH, but normal serum T4 and T3 concentrations. We do not discuss subclinical hyperthyroidism here, but it was recently reviewed in another Lancet Seminar.2

Section snippets

Epidemiology

Prevalence of hyperthyroidism is 0·8% in Europe,3 and 1·3% in the USA.4 Hyperthyroidism increases with age and is more frequent in women. The prevalence of overt hyperthyroidism is 0·5–0·8% in Europe,3 and 0·5% in the USA.4 Data for ethnic differences are scarce, but hyperthyroidism seems to be slightly more frequent in white people than in other races.3 The incidence of mild hyperthyroidism is also reported to be higher in iodine-deficient areas than in iodine-sufficient areas, and to decrease

Thyrotoxicosis with hyperthyroidism

The most common cause of hyperthyroidism in iodine-sufficient areas is Graves' disease. In Sweden, the annual incidence of Graves' disease is increasing, with 15–30 new cases per 100 000 inhabitants in the 2000s.6, 7 The cause of Graves' disease is thought to be multifactorial, arising from the loss of immunotolerance and the development of autoantibodies that stimulate thyroid follicular cells by binding to the TSH receptor. Several studies have provided some evidence for a genetic

Signs and symptoms due to excess thyroid hormones

Excess thyroid hormone affects many different organ systems (table 2). Commonly reported symptoms are palpitations, fatigue, tremor, anxiety, disturbed sleep, weight loss, heat intolerance, sweating, and polydipsia. Frequent physical findings are tachycardia, tremor of the extremities, and weight loss.21, 22, 23

Signs and symptoms specific to the underlying causes of hyperthyroidism

Signs and symptoms include ophthalmopathy, thyroid dermopathy, and thyroid acropachy in Graves' disease; globus sensation, dysphagia, or orthopnoea due to oesophageal or tracheal

Diagnosis

Serum TSH should be measured first, because it has the highest sensitivity and specificity in the diagnosis of thyroid disorders.42 If low, serum free T4 or free T4 index, and free or total T3 concentrations should be measured to distinguish between subclinical hyperthyroidism (with normal circulating hormones) and overt hyperthyroidism (with increased thyroid hormones). It also identifies disorders with increased thyroid hormone concentrations and normal or only slightly raised TSH

Treatment

The three options for treating patients with hyperthyroidism are antithyroid drugs (ATDs), radioactive iodine ablation, and surgery. All three therapeutic options would be effective in the treatment of patients with Graves' disease, whereas patients with toxic adenoma or toxic multinodular goitre should have either radioactive iodine therapy or surgery, since these patients rarely go into remission.54 In patients with toxic nodular goitre, ATDs are generally used to restore euthyroidism before

Thyroid storm

Thyroid storm is a rare disorder with an incidence of 0·2 per 100 000 person-years in Japan and occurring in 1–5% of patients admitted to hospital for thyrotoxicosis.117, 118, 119 It is an emergency with a high mortality rate of 8–25%.119, 120 The presentation does not depend on serum thyroid hormones concentrations, which are similar to compensated thyrotoxicosis. An apparent trigger can be identified in up to 70% of cases: usually unreliable use or discontinuation of ATD, followed by

Future research

Treatment of hyperthyroidism has not changed greatly in the past several decades. Choices are between long-term therapy, with risk of relapse, or destruction of the thyroid gland with subsequent hypothyroidism. ATDs are a conservative option, but have about a 50% relapse rate; however, thyroidectomy and radioactive iodine treatment are definitive therapies, but with subsequent hypothyroidism needing lifelong therapy with thyroid hormone replacement. Future research should be directed towards a

Search strategy and selection criteria

We searched MEDLINE (January, 2000, to October, 2015) and the Cochrane Library (January, 2000, to October, 2015), using the terms “hyperthyroidism” or “thyrotoxicosis” combined with the terms “Graves' disease”, “toxic adenoma”, “toxic multinodular goiter”, “thyroiditis”, “radioactive iodine therapy”, “antithyroid drugs”, “thyroidectomy”. We also used the reference lists of the selected publications identified by the search strategy and textbooks. Most of the references were selected from

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